Here we investigated the effects of KE and KS consumption on blood βHB and metabolite concentrations. As we found that KE ingestion delivered a >50% higher plasma concentrations of d-βHB alone, we subsequently determined the reliability and repeatability of ketosis following KE consumption and the effects of concomitant meal ingestion on blood ketone and substrate kinetics. Finally, we determined whether nasogastric infusion could be used for KE administration, given that some patients require feeding in this manner.

After a few days of fasting, or of drastically reduced carbohydrate consumption (below 50 g/day), glucose reserves become insufficient both for normal fat oxidation via the supply of oxaloacetate in the Krebs cycle (which gave origin to the phrase ‘fat burns in the flame of carbohydrate') and for the supply of glucose to the central nervous system (CNS).4

The metabolic phenotype of endogenous ketosis is characterized by lowered blood glucose and elevated FFA concentrations, whereas both blood glucose and FFA are lowered in exogenous ketosis. During endogenous ketosis, low insulin and elevated cortisol increase adipose tissue lipolysis, with hepatic FFA supply being a key determinant of ketogenesis. Ketone bodies exert negative feedback on their own production by reducing hepatic FFA supply through βHB-mediated agonism of the PUMA-G receptor in adipose tissue, which suppresses lipolysis (Taggart et al., 2005). Exogenous ketones from either intravenous infusions (Balasse and Ooms, 1968; Mikkelsen et al., 2015) or ketone drinks, as studied here, inhibit adipose tissue lipolysis by the same mechanism, making the co-existence of low FFA and high βHB unique to exogenous ketosis.

Over the past couple years, I’ve tried a number of ketone supplements, generally to enhance a longer fast or to offer an edge before one of my Ultimate Frisbee evenings. This Kegenix variety is one I’d recommend. I’ve also used Quest Nutrition MCT oil powder with good results as well, but there are plenty of other solid formulations to choose from.

If the goal is to deplete glucose levels so that we can start producing ketone bodies, then forcibly exerting physical energy through exercise is a great way to go about it. Keeping it relatively low intensity to begin with and working out in the morning is recommended as this helps to keep down your cortisol (stress hormone) levels. This only applies at the beginning of your keto adaptation process, as intense workouts such as HIIT once already keto-adapted will be completely fine.

Exogenous ketones are not a magical fat-loss supplement, and to suggest otherwise is both factually incorrect and deliberately misleading. In fact, consuming ketones to excess can hinder rather than help fat loss! Aggressive marketing of exogenous BHB’s has helped to create a myth being believed now by millions – that simply drinking ketones each day will somehow magically melt away the pounds. The metabolic fact that unscrupulous marketers do not point out is that dietary fat (plate fat; or fat/ketones you ingest) will be burned before stored fat (body fat). So, whilst exogenous ketones can help you to mitigate hunger (and therefore help you achieve a caloric deficit) – and although they also have many other benefits (detailed below); they are not a magic wand that you can wave to achieve weight or fat loss and should not be marketed as such.
But there have also been studies done showing that the Inuit Eskimo’s do not actually reach a state of ketosis. This is due to numerous factors. One being that the diet the eskimo’s eat ‘would not be expected to cause ketosis, because the calculated anti-ketogenic effect of the large protein ingestion was somewhat more than enough to offset the ketogenic effect of fat plus protein.”
Unless otherwise stated, statistical analysis was conducted using Prism 6™ software. Values, expressed as means ± SEM, were considered significantly different at p < 0.05. Initial tests were undertaken to ensure that normality and sphericity assumptions were not violated. Subsequently, either one or two way repeated measures ANOVA, or Freidman's test with post-hoc Tukey or Dunnet's correction were performed, to compare changing concentrations of substrates, electrolytes, pH, insulin, breath and urinary βHB: both over time and between study interventions. In Study 2, data from each of the two study visits in each condition (fed and fasted) completed by an individual were included in the analysis.
Human's ability to produce and oxidize ketone bodies arguably evolved to enhance survival during starvation by providing an energy source for the brain and slowing the breakdown of carbohydrate and protein stores (Owen et al., 1967; Sato et al., 1995; Marshall, 2010). The brain is normally reliant on carbohydrate as a substrate, being less able to metabolize lipids, despite adipose tissue representing a far larger energy store than muscle and liver glycogen. Therefore, during starvation, lipids are used for hepatic ketogenesis and, via ketone bodies, lipids sustain the brain. Endogenous production of the ketone bodies, d-β-hydroxybutyrate (βHB) and acetoacetate (AcAc), increases slowly, driven by interactions between macronutrient availability (i.e., low glucose and high free fatty acids) and hormonal signaling (i.e., low insulin, high glucagon and cortisol). Produced continuously under physiological conditions, blood ketone concentrations increase during starvation (Cahill, 1970), when consuming a “ketogenic” (low carbohydrate, high-fat) diet (Gilbert et al., 2000) or following prolonged exercise (Koeslag et al., 1980).
Some people follow more of an Ultra Low Carb diet approach. This is generally around 50g or less of carbs per day. A ULC is more supportive of reaching a ketogenic state, but again total carbs are not the only variable when it comes to reaching ketosis (other factors such as types of carbs, protein consumption, portion size, ingredients, supplements used etc. all play a role and will be covered in more detail below).
Ketones are naturally slightly acidic, so the combination of BHB with sodium acts as a bit of a buffer to this acidity. Ketones will also naturally act as a diuretic, so you lose salt, potassium calcium and magnesium, and it is generally encouraged to increase sodium intake with ketones. The addition of sodium to the product will replenish this salt loss.
Most people know that you can lose weight by consuming fewer carbs and a lot more protein. However, it's very important that you watch your protein intake carefully if you want to achieve ketosis quickly. There needs to be a balance in the amount of protein you are consuming, since too much of it is not going to be beneficial for you. What you need to remember is that this process is all about getting the right balance of fats, proteins, magnesium, salts, etc., to get your body into ketosis faster.
Appetite suppression: Appetite was measured in 10 males and 5 females after consuming a ketone ester (KE) or a dextrose (DEXT) drink . Desire to eat and perception of hunger dropped after both drinks, but the KE was 50% more effective for 1.5-4hrs. Insulin levels rose for both drinks but were 3x less with the KE drink after 30mins (Fig 2). The hunger hormone, ghrelin, was significantly lower between 2 to 4 hours after drinking the KE (Fig 2). In conclusion Ketone esters delay the onset of hunger and lower the desire to eat. 8
Other studies have found that fasting was as effective as chemotherapeutic agents in delaying progression of different tumors and increased the effectiveness of chemotherapeutic drugs against melanoma, glioma, and breast cancer cells. Although this research may not apply to your life, it does suggest that intermittent fasting can help support your body in times of toxic stress.
That’s exactly what ketones do: inhibit lipolysis, the breakdown of body fat into triglycerides and free fatty acids for burning. In normal conditions where ketones are produced endogenously, this is expected and beneficial. If homemade ketones increased lipolysis, you’d end up with ketoacidosis. You’d make ketones which released more body fat which got turned into more ketones which released more body fat which became more ketones. And on and on. It simply wouldn’t stop.
When you are in a state of ketosis, the body turns fatty acids into ketones - these appear as beta-hydroxybutyrate in the blood. Measuring blood ketones is regarded as the gold standard and most accurate way to track ketone levels. Testing this way can be expensive, its can cost up to $3 a strip, so if you're testing multiple times a day it can get pricey.

Most people know that you can lose weight by consuming fewer carbs and a lot more protein. However, it's very important that you watch your protein intake carefully if you want to achieve ketosis quickly. There needs to be a balance in the amount of protein you are consuming, since too much of it is not going to be beneficial for you. What you need to remember is that this process is all about getting the right balance of fats, proteins, magnesium, salts, etc., to get your body into ketosis faster.

I’m getting an increasing number of questions about exogenous ketones. Are they good? Do they work for performance? Is there a dose-response curve? If I’m fasting, can I consume them without “breaking” the fast? Am I in ketosis if my liver isn’t producing ketones, but my BOHB is 1.5 mmol/L after ingesting ketones? Can they “ramp-up” ketogenesis? Are they a “smart drug?” What happens if someone has high levels of both glucose and ketones? Are some products better than others? Salts vs esters? BHB vs AcAc? Can taking exogenous ketones reduce endogenous production on a ketogenic diet? What’s the difference between racemic mixtures, D-form, and L-form? What’s your experience with MCTs and C8?

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